Open heart surgery, while being performed on a daily basis across the country, is by its nature a most serious form of major surgery. Improved techniques and skills have increased the success of this operation and many patients benefit from the procedure.
One ever present problem which follows open heart surgery is post-operative bleeding. Post operative bleeding contributes to depletion of valuable blood products and significantly increases the physiologic strain experienced by the patient. But surgical bleeding is a local phenomenon, not systemic, and is best treated by local methods because systemic enhancement of the coagulation cascade can cause vein graft occlusion, valve thrombosis, phlebitis or drug toxicity. On the other hand, some coagulation enhancers cannot be given systemically or in sufficient quantities for the desired effect.
It has been observed that most patients who have undergone open heart surgery, and who are operated on again within a short time for one reason or another, exhibit no specific or localized sites of bleeding although they may have experienced significant blood loss. It is from this observation that the conclusion is reached that blood loss occurs over a relatively wide area and not localized sites, and is caused by fibrinolysis throughout the area and by the action of circulating fibrinolysins.
One compound, thrombin, has been proposed as a blood clotting preparation in U.S. Pat. No. 2,532,348, and in fact is presently an accepted treatment agent for clotting. U.S. Pat. No. 2,718,487 also teaches the effectiveness of thrombin, and proposes an improvement in which the thrombin is reacted with an acricline compound to form a reaction product. Of course the use of thrombin is not a universal cure, as disclosed in U.S. Pat. No. 4,364,861 and U.S. Pat. No. 4,391,746 where treatments specifically free of thrombin are prepared. The last two patents teach that the injection of thrombin into a human is considered highly dangerous.
The specific problem of excessive hemorrhage after cardiopulmonary bypass surgery is discussed in an article by Cary J. Lambert, MD, and others, entitled The Treatment of Postperfusion Bleeding Using E-Aminocaproic Acid, Cryoprecipitate, Fresh-Frozen Plasma, and Protamine Sulfate, published in the Annals of Thoracic Surgery, Vol. 28 No. 5, November 1979. In that article the problem of post operative bleeding is discussed. Several treatments are suggested. In the case of compensated hyperfibrinolysis (i.e., fibrinolysis without coagulation factor deficiencies) as measured by identified tests, epsilon-aminocaproic acid, AMICAR was intravenously administered. For uncompensated hyperfibrinolysis, cryoprecipitate and possibly plasma were also given. Where unneutralized heparin was detected in tests, protamine sulfate was given in an appropriate dose as determined by assay. In each case, close and rapid monitoring of the patient with rapid hematological assessment is needed.
This last mentioned cause of excessive hemorrhage, unneutralized heparin, is a problem which occurs because heparin is administered to stop the coagulation process during surgery. After surgery, treatment is needed to reverse circulating heparin and to prevent heparin rebound, which sometimes occurs with the reentry of heparin into the bloodstream from the patient's tissues. To prevent this, protamine sulfate is used to bind heparin, but this strong organic base has only been found to be effective on circulating heparin. Again, close monitoring of heparin levels is needed to provide a suitable treatment.
At present there is not a satisfactory treatment of post operative bleeding which is safe, fast, and is not dependant on time consuming laboratory tests.